Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes

Jamal Nasir, Stan B. Floresco, John R. O'Kusky, Virginia M. Diewert, Joy M. Richman, Jutta Zeisler, Anita Borowski, Jamey D. Marth, Anthony G. Phillips, Michael R. Hayden

    Research output: Contribution to journalArticle

    Abstract

    Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia. © 1995.
    Original languageEnglish
    Pages (from-to)811-823
    Number of pages13
    JournalCell
    Volume81
    Issue number5
    DOIs
    Publication statusPublished - 2 Jun 1995

    Fingerprint

    Huntington Disease
    Heterozygote
    Genes
    Subthalamic Nucleus
    Somites
    Gastrulation
    Organogenesis
    Essential Genes
    Homozygote
    Basal Ganglia
    Exons
    Motor Activity
    Display devices

    Keywords

    • Huntington's disease
    • Human gene
    • Genetics

    Cite this

    Nasir, Jamal ; Floresco, Stan B. ; O'Kusky, John R. ; Diewert, Virginia M. ; Richman, Joy M. ; Zeisler, Jutta ; Borowski, Anita ; Marth, Jamey D. ; Phillips, Anthony G. ; Hayden, Michael R. / Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. In: Cell. 1995 ; Vol. 81, No. 5. pp. 811-823.
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    abstract = "Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia. {\circledC} 1995.",
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    author = "Jamal Nasir and Floresco, {Stan B.} and O'Kusky, {John R.} and Diewert, {Virginia M.} and Richman, {Joy M.} and Jutta Zeisler and Anita Borowski and Marth, {Jamey D.} and Phillips, {Anthony G.} and Hayden, {Michael R.}",
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    Nasir, J, Floresco, SB, O'Kusky, JR, Diewert, VM, Richman, JM, Zeisler, J, Borowski, A, Marth, JD, Phillips, AG & Hayden, MR 1995, 'Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes', Cell, vol. 81, no. 5, pp. 811-823. https://doi.org/10.1016/0092-8674(95)90542-1

    Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. / Nasir, Jamal; Floresco, Stan B.; O'Kusky, John R.; Diewert, Virginia M.; Richman, Joy M.; Zeisler, Jutta; Borowski, Anita; Marth, Jamey D.; Phillips, Anthony G.; Hayden, Michael R.

    In: Cell, Vol. 81, No. 5, 02.06.1995, p. 811-823.

    Research output: Contribution to journalArticle

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    AU - Nasir, Jamal

    AU - Floresco, Stan B.

    AU - O'Kusky, John R.

    AU - Diewert, Virginia M.

    AU - Richman, Joy M.

    AU - Zeisler, Jutta

    AU - Borowski, Anita

    AU - Marth, Jamey D.

    AU - Phillips, Anthony G.

    AU - Hayden, Michael R.

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